Overall Staphylococcus aureus is a gram positive bacteria which possesses a multitude of virulence factors. It is a frequent and severe pathogen in hospitals and of increasing concern in the community, where it results in severe skin infections, pneumonia, bacterial endocarditis and sepsis. A significant proportion of these infections are the result of methicillin-resistant S. aureus (MRSA). We have developed a highly immunogenic nanoparticle vaccine capable of rapidly eliciting antibody against the pore neutralizing determinant (PND) within alpha toxin (AT), a ubiquitous and critical virulence factor of MRSA. Previous work has demonstrated that Ab against the PND is highly efficacious in preventing tissue injury and bacterial growth in a rigorous mouse dermonecrosis model, and in protecting mice in a lethal model of S. aureus pneumonia. In this project, we will develop a bivalent vaccine which targets both the PND as well as critical epitopes within both Staphylococcal enterotoxin B and C, which have been shown to be particularly important virulence factors in MRSA infections, but also have the potential to be formulated as bioweapons. The vaccine emerging from these studies will be uniquely efficacious against MRSA infections and for protection against the potential for SEB and SEC intoxication.